The objective of the proposed research is to purify and characterize a human placental-derived mitogenic activity (PDMA). PDMA is a potent growth factor that is detected in homogenized tissue and in conditioned medium of organ cultures derived from second trimester placentas. PDMA stimulates proliferation of monolayer adrenocortical cell cultures from human fetuses of the same gestational age. Crude PDMA appears to be a heat sensitive protein and resistant to the growth inhibitory effect of the pituitary steroidogenic hormone, adrenocorticotropin (ACTH). For the proposed research, primary cell cultures of human fetal adrenocortical cells will be used to assay for PDMA growth effects by DNA incorporation of [3H] thymidine and cell number quantitation. PDMA from extracted human placental tissue will be purified to homogenity by column chromatography. The physical and chemical properties and composition of purifed PDMA will be determined. The interaction of purified PDMA and ACTH will be characterized for effects on cell growth and steroid production. Polyclonal antisera to purified PDMA will be produced and characterized for antigen specificity to other polypeptide growth factors and placental hormones. The PDMA antisera will be used to determine if growth activity in placenta organ culture medium is the same as that from tissue homogenates. In vivo, the human fetal adrenal cortex is an actively growing tissue and is one of the largest fetal organs. In vitro regulation of human fetal adrenocortical cell growth by placental-derived factors would further elucidate the interaction of these two tissues known as the feto-placenta unit. Also, these studies will have implications on the an endocrine role of the placenta in the direct control of fetal growth in general.